TOPLINE

Durvalumab plus gemcitabine and cisplatin (GemCis) demonstrated sustained survival benefit in participants with advanced biliary tract cancer with a 48-month overall survival rate of 11.8% vs 4.3% for placebo plus GemCis. The treatment combination maintains a clinically manageable safety profile with no new safety signals identified after 4 years of follow-up.

METHODOLOGY

• The primary analysis of the phase 3 TOPAZ-1 study demonstrated that durvalumab plus GemCis resulted in improved overall survival in participants with advanced biliary tract cancer compared with placebo plus GemCis. This post hoc analysis represents the longest follow-up of an immunotherapy plus chemotherapy regimen in first-line advanced biliary tract cancer to date, evaluating survival, subsequent anticancer therapy use, and safety outcomes approximately 4 years after the last participant was randomized.
• A total of 685 participants with histologically confirmed unresectable, locally advanced, or metastatic biliary tract adenocarcinoma were randomly assigned in a 1:1 ratio in this global, double-blind, placebo-controlled, phase 3 trial conducted at 105 sites in 17 countries from April 2019 to December 2020.
• Participants received intravenous durvalumab 1500 mg or placebo plus gemcitabine 1000 mg/m² and cisplatin 25 mg/m² on days 1 and 8 every 3 weeks for up to eight cycles, followed by durvalumab or placebo monotherapy every 4 weeks until discontinuation criteria were met.
• Randomization was stratified by disease status (initially unresectable or recurrent) and primary tumor site (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer).
• Primary outcome measures included overall survival, duration of treatment exposure, serious adverse events (AEs), and AEs resulting in discontinuation assessed approximately 48 months after the last participant was randomized, with data cutoff on February 28, 2025.
• Median follow-up in censored participants was 56.9 months (range, 1.7-67.2 months) for the durvalumab plus GemCis arm and 50.7 months (range, 0.9-62.6 months) for the placebo plus GemCis arm.

TAKEAWAY

• Median overall survival was 13.0 months for durvalumab plus GemCis vs 11.4 months for placebo plus GemCis, with a hazard ratio of 0.75.
• The overall survival rate ratio at 48 months was 2.74, with an overall survival rate of 11.8% in the durvalumab plus GemCis arm vs 4.3% in the placebo plus GemCis arm, demonstrating sustained long-term survival benefit.
• Rates of serious AEs possibly related to treatment were similar between arms, occurring in 52 of 338 participants (15.4%) in the durvalumab plus GemCis arm vs 59 of 342 participants (17.3%) in the placebo plus GemCis arm.
• AEs leading to study drug discontinuation occurred in 21 of 338 participants (6.2%) in the durvalumab plus GemCis arm and 18 of 342 participants (5.3%) in the placebo plus GemCis arm, with no new safety signals identified at 4-year follow-up.

IN PRACTICE

“Durvalumab plus GemCis demonstrated long-term survival benefit and a clinically manageable safety profile, supporting its use as a first-line treatment for [advanced biliary tract cancer],” the authors of the study wrote.

SOURCE

The study was led by Do-Youn Oh, MD, PhD, Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. It was published online on July 9 in JAMA Oncology.

LIMITATIONS

According to the authors, all assessments in this updated analysis were exploratory with no formal statistical calculations performed. Additionally, after the 90-day safety follow-up period ending on February 24, 2022, only AEs resulting in discontinuation and serious AEs were reported. The authors noted that other limitations of the TOPAZ-1 study have been described in previous publications.

DISCLOSURES

AstraZeneca provided funding for this study and was involved in the design and conduct of the study, data collection, management, analysis, and interpretation, as well as manuscript preparation, review, approval, and the decision to submit for publication. Oh had full access to all study data and reported taking responsibility for data integrity and accuracy. Aiwu Ruth He, MD, PhD, disclosed receiving personal fees from speakers bureaus outside the submitted work. Li-Tzong Chen, MD, PhD, disclosed receiving grants from the National Science and Technology Council and the National Health Research Institutes during the study; personal fees from multiple pharmaceutical companies including ACT Genomics, Novartis, Ipsen, Ono Pharmaceutical, MSD, AstraZeneca, Revolution Medicines, BMS, Onward, Astellas, AbbVie, Taivex, and AcadeMab Biomedical; and grants from TTY Biopharm, Pfizer, and SynCore Biotechnology outside the submitted work and holding patents for anti-ENO1 and anti-CXCR2 monoclonal antibodies. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.